Ischemic stroke is one of the major causes of global mortality, which puts great demands on health systems and social welfare. Ischemic stroke is a complex pathological process involving a series of mechanisms such as ROS accumulation, Ca2+ overload, inflammation, and apoptosis. The lack of effective and widely applicable pharmacological treatments for ischemic stroke patients has led scientists to find new treatments. The use of herbal medicine, as an alternative or complementary therapy, is increasing worldwide. For centuries, our ancestors had known the remedial nature of Nigella sativa (Family Ranunculaceae) and used it in various ways, either as medicine or as food. Nowadays, N. sativa is generally utilized as a therapeutic plant all over the world. Most of the therapeutic properties of this plant are attributed to the presence of thymoquinone which is the major biological component of the essential oil. The present review describes the pharmacotherapeutic potential of N. sativa in ischemic stroke that has been carried out by various researchers. Existing literature highlights the protective effects of N. sativa as well as thymoquinone in ischemia stroke via different mechanisms including anti-oxidative stress, anti-inflammation, anti-apoptosis, neuroprotective, and vascular protective effects. These properties make N. sativa and thymoquinone promising candidates for developing potential agents for the prevention and treatment of ischemic stroke.